Effect of induction chemo-immunotherapy on the chance for re-irradiation in high-risk recurrent nasopharyngeal carcinoma: A prospective, single-arm, phase II trial.

Abstract

6040 Background: The PRANCIS model has been shown to be robust for identifying patients with recurrent nasopharyngeal carcinoma (rNPC) who are at high risk of treatment-related adverse events from re-irradiation (reRT). Here, we investigate the efficacy of combination doublet gemcitabine-cisplatin (GP) and PD-1 inhibitor (Toripalimab) to down-classify PRANCIS high risk (>252) to low-risk post-3 cycles of treatment, and the survival outcomes of these patients. For patients who converted to low-risk, reRT may be considered (NCT03930498). Methods: Eligibility criteria included diagnosed as local ± regional recurrence after ≥1 year of radical treatment, not suitable for surgery, histologic or clinically diagnosis of NPC, stage rII-IVa (AJCC/UICC 8th), PRANCIS model > 252 points. All patients received 3 cycles of GP + PD-1 inhibitor, then received reRT (GTV, 60-66Gy, 1.8-2.0Gy/f) plus PD-1 inhibitor if got CR/PR (reRT group), or received another 3 cycles of GP+PD-1 inhibitor if got SD (no reRT group), finally all got 4 cycles of PD-1 inhibitor maintenance. Primary end point was 2-year overall survival (OS). Results: Between Mar 2020 to Nov 2023, 68 high-risk patients were recruited (Table 1). After 3 cycles of GP + PD-1 inhibitor, 44 (64.7%) patients got PR (34 down-classify to low-risk and 10 still high-risk) and received full-course reRT, 22 (32.4%) got SD (all high-risk) and kept receiving GP + PD-1 inhibitor, and 2 (2.9%) could not be evaluated due to 1 died of COVID-19 and 1 withdrew after 2 cycles of treatment. 56 (82.4%) patients finished the scheduled treatment, and 12 discontinued chemo-immunotherapy. With a median follow-up time of 32.7 months, the 2-year OS of whole cohort was 67.2%, and 73.8% vs 51.2% ( P = 0.019) in reRT group vs no reRT group. The 2-year progression-free survival (PFS) of whole cohort was 47.9%, and 61.0% vs 24.3% ( P < 0.0001) in reRT group vs no reRT group. The most common ≥grade 3 toxicities included neutropenia (30.9%), lymphopenia (22.1%), and xerostomia (16.2%). The incidences of grade 3 nasopharyngeal necrosis was 5.9%. Two (2.9%) patients died of massive nasal bleeding. Conclusions: Induction chemo-immunotherapy offered the chance of reRT for high-risk rNPC patients and improved their overall survival with acceptable toxicities. Clinical trial information: NCT03930498 . Basic information. Variables Whole cohort reRT group no reRT group Age † , year 52.0 (43.0 - 58.0) 54.5 (42.8 - 58.8) 47.0 (43.0 - 54.8) Sex  Male 51 (75.0) 30 (68.2) 21 (87.5)  Female 17 (25.0) 14 (31.8) 3 (12.5) rT stage  T3 36 (52.9) 28 (63.6) 8 (33.3)  T4 32 (47.1) 16 (36.4) 16 (66.7) rN stage  N0 36 (52.9) 25 (56.8) 11 (45.8)  N1-3 32 (47.1) 19 (43.2) 13 (54.2) rTNM stage  III 35 (51.5) 27 (61.4) 8 (33.3)  IVa 33 (48.5) 17 (38.6) 16 (66.7) pre-treatment EBV DNA, copy/ml  0 23 (33.8) 14 (31.8) 9 (37.5)  >0 41 (60.2) 27 (61.4) 14 (58.3)  Missing 4 (5.9) 3 (6.8) 1 (4.2) PRANCIS model † , points 295.3 (264.1 - 321.8) 270.8 (258.1 - 340.5) 309.2 (297.5 - 319.4) † median (IQR).